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Biomedical subjects

A Lewis

Publications and source records attributed to A Lewis.

At least 19 recordsLinked to original sources

Corona mortis: an anatomical study with clinical implications in approaches to the pelvis and acetabulum.

The "corona mortis" is an anatomical variant, an anastomosis between the obturator and the external iliac or inferior epigastric arteries or veins. It is located behind the superior pubic ramus at a variable distance from the symphysis pubis (range 40-96 mm). The name "corona mortis" or crown of death testifies to the importance of this feature, as significant hemorrhage may occur if accidentally cut and it is difficult to achieve subsequent hemostasis. It constitutes a hazard for orthopedic surgeons especially in the anterior approach to the acetabulum. We carried out forty cadaver dissections (80 hemi-pelvises) through the ilioinguinal approach. A vascular anastomosis was found in 83% of specimens. Of these, 60% had a large diameter (>3 mm) channel along the posterior aspect of the superior pubic ramus. In clinical practice, however, 492 anterior approaches (to the best of our knowledge the largest series described) have been carried out over the last 15 years by the senior author (MB) and only five of these problematic vessels were discovered, and in only two cases was there troublesome bleeding. This study confirms a paradox: in anatomical dissections a large vessel was identified behind the superior pubic ramus, whereas in clinical practice this vessel does not seem to be as great a threat as initially perceived. Orthopedic surgeons planning an anterior approach to the acetabulum, such as the ilioinguinal or the intrapelvic approach (modified Stoppa), have to be cautious when dissecting near the superior pubic ramus. Despite the high prevalence of these large retropubic vessels in the dissecting room, surgeons should exercise caution but not alter their surgical approach for fear of excessive hemorrhage.

Acetabulum↗

Monoamine oxidase and tobacco dependence.

Tobacco smoking is a leading cause of preventable death around the world, and there are major public health and research efforts in many countries aimed at reducing its usage. However, the molecular mechanisms underlying tobacco dependence are still not completely understood. Nicotine's action on nicotinic acetylcholine receptors, and the downstream release of dopamine, is believed to be the major pathway underlying tobacco dependence. However there is mounting evidence indicating that non-nicotinic components of tobacco smoke also play a role by inhibiting monoamine oxidase (MAO) and subsequently altering neurotransmitter levels. This article provides a review of the current knowledge of the association between MAO and tobacco dependence and suggests that further research into this topic is likely to lead to more effective pharmacotherapies for smoking cessation.

Animals↗

Epigenetics and imprinting of the trophoblast -- a workshop report.

Genomic imprinting is a remarkable process that causes genes to be expressed or repressed depending on their parental-origin. Imprinted genes play important roles in prenatal growth and organ development. Postnatally, imprinted genes can contribute to the regulation of metabolic pathways and behaviour associated with the control of resources. One of the most important sites of imprinted gene action is the placenta. During this workshop at the 11th meeting of the International Federation of Placenta Associations/European Placenta Group held in Glasgow, a series of short talks were presented providing an overview of the evolution, function and mechanisms of imprinting in mammals with particular reference to the placenta. In addition, epigenetic control of trophoblast development and function were considered. This report summarises the contributions to the workshop.

Animals↗

How imprinting centres work.

Imprinted genes tend to be clustered in the genome. Most of these clusters have been found to be under the control of discrete DNA elements called imprinting centres (ICs) which are normally differentially methylated in the germline. ICs can regulate imprinted expression and epigenetic marks at many genes in the region, even those which lie several megabases away. Some of the molecular and cellular mechanisms by which ICs control other genes and regulatory regions in the cluster are becoming clear. One involves the insulation of genes on one side of the IC from enhancers on the other, mediated by the insulator protein CTCF and higher-order chromatin interactions. Another mechanism may involve non-coding RNAs that originate from the IC, targeting histone modifications to the surrounding genes. Given that several imprinting clusters contain CTCF dependent insulators and/or non-coding RNAs, it is likely that one or both of these two mechanisms regulate imprinting at many loci. Both mechanisms involve a variety of epigenetic marks including DNA methylation and histone modifications but the hierarchy of and interactions between these modifications are not yet understood. The challenge now is to establish a chain of developmental events beginning with differential methylation of an IC in the germline and ending with imprinting of many genes, often in a lineage dependent manner.

Animals↗

Biological activity of residual cell-substrate DNA.

Vaccines and other biological products manufactured in cells contain contaminating residual DNA derived from that production cell substrate, with the amount and form of this DNA depending mainly on the type of vaccine. The potential risk of this cellular DNA has been debated for over 40 years without resolution. Opinions on residual DNA have varied from it being considered an inert contaminant, and thus its presence should not be deemed to be a risk to vaccine recipients, to it being considered an important risk factor, particularly for vaccines manufactured in certain cell substrates, such as cells derived from tumours or cells that are tumorigenic. We are not of the opinion that DNA can be considered biologically inert, but whether or what risk residual cell-substrate DNA poses remains to be determined. In this paper, we discuss our approaches to address this issue and describe some preliminary work.

Carcinogens↗

Penetration of tritium (as tritiated water vapour) into low carbon steel and remediation using abrasive cleaning.

The UKAEA Winfrith site is in a phase of accelerated decommissioning and de-licensing which will generate significant volumes of metal wastes some of which may be suitable for disposal as exempt wastes. If contamination is present, it is often confined within the surface layers of the metal. The UKAEA Winfrith site operates a shot-blast facility (WACM) that removes paint and surface contamination from low carbon steel enabling surface contaminated painted metal to be processed and therefore certified as exempt. A study was conducted to determine whether tritium (as tritiated water vapour) has penetrated into the metal to levels exceeding the Radioactive Substances Act (1993), Substances of Low Activity (SoLA) Exemption Order criteria, and whether processing via the WACM removes sufficient tritium contamination that the SoLA Exemption Order criteria can be met. The results of sampling and analysis show that the tritium is mainly held in the paint or outer 40 microm layer of the metal and that processing through the WACM removes these layers along with sufficient tritium to meet the SoLA Exemption Order criteria.

Carbon↗

Characterization of a vaccinia virus strain used to produce smallpox vaccine in Argentina between 1937 and 1970.

Due to recent political developments, smallpox has re-emerged as a serious threat. We recovered and characterized an old batch of smallpox vaccine, Malbrán strain, produced between 1945 and 1949. The virus was re-isolated and characterized by sequence analysis and biological activity in animals. Phylogenetic analysis using the hemagglutinin and A45R genes showed that the Malbrán strain was closely related to the Lister strain of vaccinia virus. In animals, the Malbrán strain exhibited low pathogenicity, confirming historical records. Mice immunized with the Malbrán strain survived a lethal challenge with cowpox virus. Thus, this strain of vaccinia virus remains a viable candidate as a smallpox vaccine.

Argentina↗

Wavelength- and time-dependence of potentiometric non-linear optical signals from styryl dyes.

Second harmonic generation (SHG) imaging microscopy is an important emerging technique for biological research, complementing existing one- and two-photon fluorescence (2PF) methods. A non-linear phenomenon employing light from mode-locked Ti:sapphire or fiber-based lasers, SHG results in intrinsic optical sectioning without the need for a confocal aperture. Furthermore, as a second-order process SHG is confined to loci lacking a center of symmetry, a constraint that is readily satisfied by lipid membranes with only one leaflet stained by a dye. Of particular interest is "resonance-enhanced" SHG from styryl dyes in cellular membranes and the possibility that SHG is sensitive to transmembrane potential. We have previously confirmed this, using simultaneous voltage-clamping and non-linear imaging of cells to find that SHG is up to four times more sensitive to potential than fluorescence. In this work, we have extended these results in two directions. First, with a range of wavelengths available from a mode-locked Ti:sapphire laser and a fiber-based laser, we have more fully investigated SHG and 2PF voltage-sensitivity from ANEP and ASTAP chromophores, obtaining SHG sensitivity spectra that are consistent with resonance enhancements. Second, we have modified our system to coordinate the application of voltage-clamp steps with non-linear image acquisition to more precisely characterize the time dependence of SHG and 2PF voltage sensitivity, finding that, at least for some dyes, SHG responds more slowly than fluorescence to changes in transmembrane potential.

Fiber Optic Technology↗

Assessing the cellular transmembrane electrical potential difference on the hepatic uptake of palmitate.

Understanding the driving forces for the hepatic uptake of endogenous and exogenous substrates in isolated cells and organs is fundamental to describing the underlying hepatic physiology/pharmacology. In this study we investigated whether uptake of plasma protein-bound [3H]-palmitate across the hepatocyte wall is governed by the transmembrane electrical potential difference (PD). Uptake was studied in isolated hepatocytes and isolated perfused rat livers (IPL). Protein-binding and vasoactive properties of the different perfusates were determined using in vitro heptane/buffer partitioning studies and the multiple indicator dilution (MID) technique in the IPL, respectively. Altering hepatocyte PD by perfusate ion substitution resulted in either a substantial depolarization (-14 +/- 1 mV, n = 12, mean +/- S.E., substituting choline for Na+) or hyperpolarization (-46 +/- 3 mV, n = 12, mean +/- S.E., substituting nitrate for Cl-). Perfusate ion substitution also affected the equilibrium binding constant for the palmitate-albumin complex. IPL studies suggested that, other than with gluconate buffer, hepatic [3H]-palmitate extraction was not affected by the buffer used, implying PD was not a determinant of extraction. [3H]-Palmitate extraction was much lower (p < 0.05) when gluconate was substituted for Cl- ion. This work contrasts with that for the extraction of [3H]-alanine where hepatic extraction fraction was significantly reduced during depolarization. Changing the albumin concentration did not affect hepatocyte PD, and [3H]-palmitate clearance into isolated hepatocytes was not affected by the buffers used. MID studies with vascular and extravascular references revealed that, with the gluconate substituted buffer, the extravascular volume possibly increased the diffusional path length thus explaining reduced [3H]-palmitate extraction fraction in the IPL.

Alanine↗

Understanding obstacles to the recognition of and response to dementia in different European countries: a modified focus group approach using multinational, multi-disciplinary expert groups.

Experts from eight European countries (Belgium, France, The Netherlands, Ireland, Italy, Portugal, Spain and the United Kingdom) and the disciplines of clinical psychology, general practice, geriatric medicine, old age psychiatry, medical sociology, nursing and voluntary body organisation met in 2003 to explore obstacles to recognition of and response to dementia in general practice within Europe. A modified focus group methodology was used in this exploratory process. Groups were conducted over a two-day period, with five sessions lasting 1-1.5 hours each. An adapted nominal group method was used to record themes arising from the group discussion, and these themes were used in a grounded theory approach to generate explanations for delayed recognition of and response to dementia. The overarching theme that arose from the focus groups was movement, which had three different expressions. These were: population movement and its consequences for localities, services and professional experience; the journey of the person with dementia along the disease process; and the referral pathway to access services and support. Change is the core issue in dementia care, with multiple pathways of change that need to be understood at clinical and organisational levels. Practitioners and people with dementia are engaged in managing emotional, social and physical risks, making explicit risk management a potentially important component of dementia care. The boundary between generalist and specialist services is a particular problem, with great potential for dysfunctionality. Stigma and ageism are variably distributed phenomena both within and between countries.

Aged↗

Seasonal occurrence of impetigo: a retrospective 8-year review (1996-2003).

Impetigo, a common skin infection, has shown seasonal variation in African, Australian and Indian studies. We investigated seasonal variation of impetigo in a UK paediatric population. A total of 1552 children with impetigo were seen in the Accident and Emergency (A&E) department between 1996 and 2003. The number of impetigo cases was always higher in late summer than in winter, and furthermore, increased year on year. These changes could not be accounted for by variation in total patient numbers seen in A&E, and suggest a correlation between impetigo frequency and climatic temperature. Possible reasons for these findings include exposed skin due to loose clothing in the summer leading to more skin-to-skin contact and minor trauma.

Child↗

Outdoor carbon monoxide, nitrogen dioxide, and sudden infant death syndrome.

AIMS: To investigate whether infants who died of SIDS were more likely to have higher acute and lifetime average exposures to outdoor carbon monoxide (CO) and nitrogen dioxide (NO2) than comparison healthy infants. METHODS: A total of 169 case and 169 matched control infants born between 1988 and 1992, were studied. CO and NO2 concentrations, averaged for all days within the infant's lifespan, and the last 30 days, 7 days, 3 days, and 1 day of life were obtained from air pollutant data provided by the California Air Resources Board. RESULTS: Based on monthly aggregated data, average CO and particularly NO2 were associated with SIDS count, even after adjustment for seasonal trends. SIDS outcome was not significantly associated with high average outdoor CO levels for any time period. However, high average outdoor NO2 levels on the last day of the infant's exposure period were significantly associated with SIDS; the adjusted odds ratio was 2.34 (95% CI 1.13 to 4.87). CONCLUSIONS: SIDS may be related to high levels of acute outdoor NO2 exposure during the last day of life. Further studies are needed to replicate this finding.

Air Pollutants↗

Displacement of the common peroneal nerve in posterolateral corner injuries of the knee.

We reviewed the relationship between the pattern of damage to the posterolateral corner of the knee and the position of the common peroneal nerve in 54 consecutive patients with posterolateral corner disruption requiring surgery. We found that 16 of the 18 patients with biceps avulsions or avulsion-fracture of the fibular head had a displaced common peroneal nerve. The nerve was pulled anteriorly with the biceps tendon. None of the 34 proximal injuries resulted in an abnormal nerve position. Whenever bone or soft-tissue avulsion from the fibular head is suspected, the surgeon should expect an abnormal position of the common peroneal nerve and appreciate the increased risk of iatrogenic damage.

Fibula↗

Inducible upregulation of oestrogen receptor-beta1 affects oestrogen and tamoxifen responsiveness in MCF7 human breast cancer cells.

To investigate the effect of altered oestrogen receptor (ER)alpha and ERbeta expression on oestrogen and anti-oestrogen action in breast cancer, we have stably expressed an inducible ERbeta1 in MCF7 breast cancer cells. Stably expressing clones were isolated and over-expression of ERbeta1 correlated with increased levels of specific radiolabelled oestradiol (E2) binding. Increased ERbeta1 did not affect endogenous levels of ERalpha but increased progesterone receptor (PR) levels. Over-expression of ERbeta1 reduced growth responses to E2 in contrast to little if any effect of over-expression of ERalpha. In oestrogen-replete conditions, over-expression of ERbeta1 but not ERalpha reduced proliferation. Over-expression of ERbeta1 did not result in anti-oestrogen resistance but was associated with increased sensitivity to 4-hydroxytamoxifen. Our results suggested that over-expression of ERbeta1 in the presence of an endogenously expressed ERalpha was associated with tamoxifen sensitivity but may negatively modulate ERalpha-mediated growth. However, not all ERalpha activities were inhibited since endogenous PR expression was increased by both ERalpha and ERbeta1 over-expression. These data paralleled those seen in some in vivo studies showing a relationship between PR and ERbeta expression as well as ERbeta expression and tamoxifen sensitivity of ER-positive breast cancer patients. These models are relevant and will be useful for dissecting the role of ERbeta1 expression in ER-positive breast cancer.

Anti-Bacterial Agents↗

Cataract surgery and subtype in a defined, older population: the SEECAT Project.

AIM: To describe the distribution of cataract subtypes present before surgery among a defined population of older, bilaterally pseudophakic individuals. METHODS: This was a cohort study of bilaterally pseudophakic individuals participating in the Salisbury Eye Evaluation (SEE), and their locally resident siblings. Subjects underwent slit lamp and retroillumination photography and grading using the Wilmer Cataract Grading System. For all individuals determined to be bilaterally pseudophakic, an attempt was made to determine for each eye the type(s) of cataract present before surgery, based on previous SEE photographs (for SEE participants) and/or medical records obtained from the operating ophthalmologist (for both SEE participants and their siblings). RESULTS: The mean age of 223 participants providing data in this study was 78.7 (SD 5.2) years, 19.3% of subjects were black and 60.1% female. The most common surgically removed cataract subtype in this population was pure nuclear (43.5%), followed by nuclear combined with posterior subcapsular cataract (PSC) (20.6%), and nuclear combined with cortical (13.9%); less common types were pure cortical (4.9%), pure PSC (4.5%), and PSC combined with cortical (2.7%). Factors such as sex and source of lens data (study photograph versus clinical record) did not significantly affect the distribution of lens opacity types, while PSC was significantly (p = 0.01) more common among younger people and nuclear cataract was significantly (p = 0.001) more common among white compared to black people. CONCLUSION: Epidemiological studies have suggested that the different subtypes of cataract are associated with different risk factors. As studies begin to identify new prevention strategies for cataract, it would appear likely that different strategies will be efficacious against different types of cataract. In this setting, it will be helpful to know which cataract types are most frequently associated with surgery. Among this older, majority white population, nuclear cataract showed a clear predominance among individuals having undergone surgery in both eyes. This may be contrasted with both clinic and population based studies of younger people, which have generally found PSC cataract to predominate.

Age Distribution↗

Acute hypoxia occludes hTREK-1 modulation: re-evaluation of the potential role of tandem P domain K+ channels in central neuroprotection.

The human tandem P domain K+ channel hTREK-1 (KCNK2) is distributed widely through the CNS. Here, whole-cell patch clamp recordings were employed to investigate the effects of hypoxia on hTREK-1 channels stably expressed in human embryonic kidney cells. Acute hypoxia caused a rapid and reversible inhibition of whole-cell K+ current amplitudes; this was PO2 dependent with a maximal inhibition achieved at 60 mmHg and below. In accordance with previous studies, hTREK-1 current amplitudes were enhanced by arachidonic acid. This effect was concentration dependent, with maximal enhancement observed at a concentration of 10 microM. Membrane deformation by the crenator trinitrophenol (to mimic cell swelling) or the cup former chlorpromazine (to mimic cell shrinkage) caused robust activation and inhibition of currents, respectively. However, current augmentation by either arachidonic acid or trinitrophenol was completely prevented during hypoxia; conversely, hypoxia blunted the inhibitory action of chlorpromazine. The abilities of arachidonic acid to augment currents and of hypoxia to completely abrogate this effect were also observed in cell-attached patches. Our data indicate that hypoxia interacts with hTREK-1, and occludes its modulation by arachidonic acid and membrane deformation. These findings also suggest that the potential neuroprotective role of TREK channels, which has recently been proposed, requires reconsideration since hTREK-1 activation is unlikely when ambient PO2 is below 60 mmHg - a situation which normally pertains in the CNS even during systemic normoxia.

Arachidonic Acid↗